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Toll-like receptor 4 mediates vascular remodeling in hyperhomocysteinemia

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Abstract

Although hyperhomocysteinemia (HHcy) is known to promote downstream pro-inflammatory cytokine elevation, the precise mechanism is still unknown. One of the possible receptors that could have significant attention in the field of hypertension is toll-like receptor 4 (TLR-4). TLR-4 is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. Its mutation can attenuate the effects of HHcy-mediated vascular inflammation and mitochondria- dependent cell death that suppresses hypertension. In this review, we observed that HHcy induces vascular remodeling through immunological adaptation, promoting inflammatory cytokine up-regulation (IL-1β, IL-6, TNF-α) and initiation of mitochondrial dysfunction leading to cell death and chronic vascular inflammation. The literature suggests that HHcy promotes TLR-4-driven chronic vascular inflammation and mitochondria-mediated cell death inducing peripheral vascular remodeling. In the previous studies, we have characterized the role of TLR-4 mutation in attenuating vascular remodeling in hyperhomocysteinemia. This review includes, but is not limited to, the physiological synergistic aspects of the downstream elevation of cytokines found within the vascular inflammatory cascade. These events subsequently induce mitochondrial dysfunction defined by excessive mitochondrial fission and mitochondrial apoptosis contributing to vascular remodeling followed by hypertension.

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Acknowledgements

This work was in part supported by NIH Grant: HL-74185.

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    1. Department of Physiology, School of Medicine, Health Sciences Centre, University of Louisville, A-1215, 500, South Preston Street, Louisville, KY, 40202, USA

      Anastasia Familtseva, Nevena Jeremic, George H. Kunkel & Suresh C. Tyagi

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    1. Anastasia Familtseva
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    2. Nevena Jeremic
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    3. George H. Kunkel
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    Correspondence to Nevena Jeremic.

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    Anastasia Familtseva and Nevena Jeremic have contributed equally to this work.

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    Familtseva, A., Jeremic, N., Kunkel, G.H. et al. Toll-like receptor 4 mediates vascular remodeling in hyperhomocysteinemia. Mol Cell Biochem 433, 177–194 (2017). https://doi.org/10.1007/s11010-017-3026-9

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